Objective This study aims to find the mechanism of salidroside on reducing sepsis induced lung injury. Methods One hundred and twenty ICR mice were divided by random number table method into 4 groups (n=30): control group (CON group), sepsis group (CLP group), sepsis+30 mg/kg salidroside (Sal‑L group) and sepsis+60 mg/kg salidroside (Sal‑H group). Survival rates of fifteen mice in each group were observed for 7 d while the remaining mice were sacrificed 24 h after model making. The lung tissues were collected. Hematoxylin‑eosin (H‑E) staining of the lung tissues, acute lung injury score (LIS) and wet/dry ratio (W/D) were evaluated. Tumor necrosis factor‑α (TNF‑α) and interleukin (IL)‑6, IL‑1β were detected by enzyme‑linked immunosorbent assay (ELISA). Western blot was used to measure phosphorylation of nuclear factor‑κB (p‑NF‑κB) protein. Results The 7‑day survival rate of mice in the CON group was 100%, whereas the survival rates were 13.33%, 50.00% and 53.33% in the CLP group, in the Sal‑L group and in the Sal‑H group respectively. The survival rates of Sal‑L group and Sal‑H group were statistically significant different with CON group and CLP group (P<0.05), but there was no statistically significant difference in survival rate between Sal‑L group and Sal‑H group (P>0.05). Compared with the CLP group, W/D, the LIS, the expression levels of TNF‑α, IL‑6, IL‑1β in the Sal‑L and Sal‑H groups were significantly decreased (P<0.01). The expression levels of TNF‑α, IL‑6 and IL‑1β of the Sal‑H group were lower than those levels in the Sal‑L group (P<0.01). The expression levels of p‑NF‑κB protein in Sal‑L group and Sal‑H group were significantly lower than the level in CLP group. Conclusions Salidroside effectively reduces the inflammatory cells aggregation in the lung tissues of the mice probably through the NF‑κB signaling pathway. It also eliminates pulmonary edema, reduces the expression levels of TNF‑α, IL‑6, and IL‑1β, which leads to increased survival rate of mice suffered from sepsis.